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Cannabinoid 2 Receptor- and Beta Arrestin 2-Dependent Upregulation of Serotonin 2A Receptors
Franklin, Jade M. Vasiljevik, Tamara Prisinzano, Thomas E. Carrasco, Gonzalo A.
Franklin, Jade M.
Vasiljevik, Tamara
Prisinzano, Thomas E.
Carrasco, Gonzalo A.
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Abstract
Recent evidence suggests that cannabinoid receptor agonists may regulate serotonin 2A (5-HT2A) receptor neurotransmission in the brain, although no molecular mechanism has been identified. Here, we present experimental evidence that sustained treatment with a non-selective cannabinoid agonist (CP 55,940) or selective CB2 receptor agonists (JWH 133 or GP 1a) upregulate 5-HT2A receptors in a neuronal cell line. Furthermore, this cannabinoid receptor agonist-induced upregulation of 5-HT2A receptors was prevented in cells stably transfected with either CB2 or β-Arrestin 2 shRNA lentiviral particles. Additionally, inhibition of clathrin-mediated endocytosis also prevented the cannabinoid receptor-induced upregulation of 5-HT2A receptors. Our results indicate that cannabinoid agonists might upregulate 5-HT2A receptors by a mechanism that requires CB2 receptors and β-Arrestin 2 in cells that express both CB2 and 5-HT2A receptors. 5-HT2A receptors have been associated with several physiological functions and neuropsychiatric disorders such as stress response, anxiety & depression and schizophrenia. Therefore, these results might provide a molecular mechanism by which activation of cannabinoid receptors might be relevant to some cognitive and mood disorders in humans.
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Date
2012-07-28
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Elsevier
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Keywords
Cannabinoids, CB2 receptors, Serotonin, Marijuana, β-Arrestins, Receptor internalization, 5-HT2A receptor
Citation
Franklin, J.m., T. Vasiljevik, T.e. Prisinzano, and G.a. Carrasco. "Cannabinoid 2 Receptor- and Beta Arrestin 2-dependent Upregulation of Serotonin 2A Receptors." European Neuropsychopharmacology 23.7 (2013): 760-67.